Management of
ovarian cancer still requires improvements in therapeutic options. A drug delivery strategy was tested that allows specific targeting of
tumor cells in combination with a controlled release of a cytotoxic molecule. To this aim, the efficacy of a loco-regional intraperitoneal treatment with a bioconjugate (
ONCOFID-S) derived by chemical linking of
SN-38, the active metabolite of
irinotecan (CPT-11), to
hyaluronan was assessed in a mouse model of ovarian
carcinomatosis. In vitro, the bioconjugate selectively interacted with
ovarian cancer cells through the CD44 receptor, disclosed a dose-dependent
tumor growth inhibition efficacy comparable to that of free
SN-38 drug, and inhibited
Topoisomerase I function leading to apoptosis by a mechanism involving
caspase-3 and -7 activation and PARP cleavage. In vivo, the intraperitoneal administration of
ONCOFID-S in
tumor-bearing mice did not induce
inflammation, and evidenced an improved therapeutic efficacy compared with
CPT-11. In conclusion,
SN-38 conjugation to
hyaluronan significantly improved the profile of in vivo tolerability and widened the field of application of
irinotecan. Therefore, this approach can be envisaged as a promising therapeutic strategy for loco-regional treatment of
ovarian cancer.